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Humberto J Vidaillet

Publications and source records attributed to Humberto J Vidaillet.

6 recordsLinked to original sources

Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database).

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were <65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (<65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.

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A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data.

BACKGROUND: Rapid genetic screening for cytochrome P450 (CYP) 2C9 variants may play a role in improving the efficacy and safety of warfarin in individuals with CYP2C9 variants. The feasibility of prospective CYP2C9 model-based warfarin dosing has not yet been assessed. OBJECTIVES: To evaluate the feasibility of applying a CYP2C9 gene-based warfarin dosing model in clinical practice. DESIGN: Prospective, randomized, single-blinded clinical pilot trial. SETTING: Large multispecialty group practice. PATIENTS: Candidates were recruited from a list of clinic patients eligible for warfarin initiation. This included patients with newly diagnosed thromboembolic disease or atrial arrhythmia, as well as patients anticipating elective valvuloplasty or arthroplasty. Patients who previously received warfarin were excluded. INTERVENTIONS: Subjects were randomized to receive either 1) a standard initiation dose of 5 mg warfarin/day, or 2) rapid CYP2C9 genotyping and an initiation dose determined using parameters estimated from a previously published multivariate model [including age, body size, co-morbidity (e.g., diabetes), clinical indication (e.g., valvuloplasty) and CYP2C9 genotype]. MEASUREMENTS: Primary outcome measurements were patient willingness to participate, physician willingness to refer, sample processing time, ability to administer calculated dosage and adequacy of follow-up. LIMITATIONS: This pilot trial was designed to assess the feasibility of model-based warfarin dosing. Power was insufficient for statistical comparison of adverse event rates. RESULTS: Forty-three of 117 patients had no prior warfarin treatment and were eligible. Five declined to participate. Twenty patients were randomized to a standard initiation dose of 5 mg daily. Eighteen patients were randomized to model-based dosing. All but one participant received the assigned initiation dose. Blood draw to dosage calculation time (including genotyping) required approximately 4 hours. Six adverse events occurred within the standard dosing group, and two adverse events occurred within the model-based dosing group. CONCLUSIONS: Prospective application of a multivariate CYP2C9 gene-based warfarin dosing model is feasible.

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Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time during the first 30 days of warfarin therapy.

OBJECTIVES: To characterize the impact of several important clinical variables on the rate of anticoagulation during warfarin initiation (i.e., the first 30 days). DESIGN: Retrospective study. SETTING: An anticoagulation service of a large horizontally integrated, multispecialty group practice in central and northern Wisconsin. PARTICIPANTS: Patients with sufficient laboratory data obtained during the initiation phase of warfarin treatment. METHODS: Patients were consented and genotyped for cytochrome P450 (CYP) 2C9 polymorphisms. Anticoagulation laboratory data were then electronically abstracted and fitted to a logistic growth model. Rate of anticoagulation was compared between groups. RESULTS: During warfarin initiation, the mean slope for rise in International Normalized Ratio (INR) of prothrombin time was significantly associated with age (p = 0.03, n = 166). Because a relationship between diabetes and warfarin dosing has been suggested previously, we assessed the impact of this comorbidity in our model as well. Diabetes showed relatively little impact, but concomitant treatment with an anti-diabetic sulfonylurea medication was associated with an increase in slope (3-fold, p < 0.05). Since this drug interaction may occur at the level of CYP2C9, we also assessed the impact of CYP2C9 genotype in our model. The impact of CYP2C9 genotype was marginally significant (p = 0.119, non-pooled dataset; p = 0.053, data pooled for CYP2C9 *2/*2, *2/*3 and *3/*3). CONCLUSIONS: Age and concomitant sulfonylurea therapy alter the rate of anticoagulation during the first 30 days of warfarin therapy.

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Familial atrioventricular nodal reentry tachycardia.

Dual atrioventricular nodal pathways, the substrate responsible for atrioventricular node reentry tachycardia (AVNRT), are thought to be randomly occurring congenital anomalies. This article describes 14 patients in six families, each with two or three first-degree relatives with paroxysmal supraventricular tachycardia. Electrophysiological evidence of dual atrioventricular nodal pathways was established in all 13 patients studied, AVNRT was induced in 12 (92%), and radiofrequency ablation of the slow pathway was curative in all cases. The data suggest a hereditary contribution to the development of atrioventricular nodal pathways and AVNRT. The pattern of inheritance appears to be autosomal dominant.

Adolescent↗

Hyperventilation-induced syncope: no need to panic.

Accurately diagnosing and treating adult patients presenting with recurrent syncope can be extremely problematic. We present the case of a patient who presented with recurrent syncope. We propose that many cases currently classified as idiopathic may in fact be due to orthostatic hypotension secondary to hyperventilation, or simply hyperventilation-induced syncope. The presence of undiagnosed psychiatric disorders should be considered in these patients.

Adult↗

Rate control vs. rhythm control in the management of atrial fibrillation in elderly persons.

Antiarrhythmic medications used to maintain sinus rhythm have long been the treatment of choice in atrial fibrillation. The results of five prospective randomized trials comparing the efficacy and safety of rhythm-control to rate-control strategies are now available. Reflecting the epidemiology of atrial fibrillation in the real world, most subjects enrolled in these investigations were elderly persons at increased risk of stroke or death. All of these trials have had similar results; these studies have failed to demonstrate a clear advantage of one treatment strategy over the other. A prespecified subgroup analysis among 3091 elderly patients in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study revealed that rhythm control was associated with a higher risk of death than rate control. This review examines developments leading to and the implications and limitations of these trials and discusses recently issued practice guidelines and the justification for ongoing efforts to develop nonpharmacologic approaches to rhythm management in atrial fibrillation.

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